In the past year, we have described a new clinical syndrome associated with hyperprolactinemia. The affected women have high prolactin levels and minimal clinical symptoms. The predominant prolactin species in their circulation is a 150 kilodalton prolactin variant which has reduced biologic activity in a NB2 rat lymphoma bioassay system. Hence, "macroprolactinemia" has to be considered in the patient with high prolactin levels who is being evaluated for the presence of a pituitary tumor. We have also acquired data which suggest that prolactin secretion from pituitary tissue removed from patients with prolactinomas is resistant to inhibition by dopamine, if in vivo testing suggests resistance. In addition, in a rodent pituitary cell line as well as in normal rodent pituitary cells, we have documented the importance of the calcium channel and calmodulin in basal and stimulated prolactin release. (C)